tbuckley/cabot-search huggingface dataset:
Efficacy of <i>Bifidobacterium longum</i> alone or in multi-strain probiotic formulations during early life and beyond
Authors: Susan Mills, Bo Yang, Graeme J. Smith, Catherine Stanton, R. Paul Ross
Journal: Gut Microbes (2023)

The significance of Bifidobacterium to human health can be appreciated from its early colonization of the neonatal gut, where Bifidobacterium longum represents the most abundant species. While its relative abundance declines with age, it is further reduced in several diseases. Research into the beneficial properties of B. longum has unveiled a range of mechanisms, including the production of bioactive molecules, such as short-chain fatty acids, polysaccharides, and serine protease inhibitors. From its intestinal niche, B. longum can have far-reaching effects in the body influencing immune responses in the lungs and even skin, as well as influencing brain activity. In this review, we present the biological and clinical impacts of this species on a range of human conditions beginning in neonatal life and beyond. The available scientific evidence reveals a strong rationale for continued research and further clinical trials that investigate the ability of B. longum to treat or prevent a range of diseases across the human lifespan.
PSMA-positive Circulating Tumor Cell Detection and Outcomes with Abiraterone or Enzalutamide Treatment in Men with Metastatic Castrate-resistant Prostate Cancer
Authors: Santosh Gupta, Susan Halabi, Qian Yang, Akash Roy, Alisa Tubbs, Yamini Gore, Daniel J. George, David M. Nanus, Emmanuel S. Antonarakis, Daniel C. Danila, Russell Z. Szmulewitz, Richard Wenstrup, Andrew J. Armstrong
Journal: Clinical Cancer Research (2023)

Abstract Purpose: In men with metastatic castration-resistant prostate cancer (mCRPC), prostate-specific membrane antigen (PSMA)-targeted radioligand therapy has drastically improved clinical outcomes. A liquid biopsy characterizing PSMA expression could be useful in guiding optimal therapy. Experimental Design: We conducted a retrospective analysis of the prospective multicenter PROPHECY (Prospective CiRculating PrOstate Cancer Predictors in HighEr Risk mCRPC StudY) trial of men with mCRPC (n = 118) treated with abiraterone (abi) or enzalutamide (enza). Circulating tumor cells (CTC) were enriched (CTC/mL) and characterized for PSMA protein expression/heterogeneity at baseline and progression. We utilized proportional hazards modeling of the association between PSMA-positive (PSMA+) CTC enumeration with overall survival (OS) and progression-free survival (PFS). Results: Overall, 97 men with mCRPC had evaluable blood samples for baseline CTC PSMA detection; 78 men (80%) had detectable CTCs. Of these, 55% (43/78) of men had any PSMA CTC detection, 21% (16/78) had ≥2 PSMA+ CTCs/mL, and 19% (8/43) were 100% PSMA+. At progression on abi/enza, 88% (50/57) of men had detectable CTCs, 68% (34/50) had any PSMA CTCs, and 12% (4/34) had 100% PSMA+ CTCs. Among paired cases (n = 57), PSMA+ CTC detection increased slightly after abi/enza progression. Using an optimal cutoff of ≥2 PSMA+ CTCs/mL, median OS was 26, 21, and 11 months for men without CTCs, PSMA− CTCs, and PSMA+ CTCs. Adjusting for prior abi/enza therapy, Halabi clinical risk score, and CTC enumeration, the HRs for OS and PFS for PSMA+ CTC+ were 3.0 [95% confidence interval (CI) = 1.1–7.8] and 2.3 (95% CI = 0.9–5.8). Conclusions: We observed PSMA CTC heterogeneity between and within patients with mCRPC over time during abi/enza progression. CTC PSMA enumeration was adversely prognostic independent of clinical factors and disease burden. Further validation is warranted in the context of PSMA-targeted therapies.
Reply: Portal hypertension and variceal bleeding in patients with liver cancer: Evidence gaps for prevention and management
Authors: Manon Allaire, Dominique Thabut
Journal: Hepatology (2023)

We thank Tripathi and colleagues for their interest in our review about the evidence gaps for the prevention and management of portal hypertension (PHT) and acute variceal bleeding in patients with HCC.1 We agree that we are facing a lack of strong evidence regarding the use of nonselective beta-blockers (NSBB) in HCC patients with a liver stiffness measurement ≥25 kPa. However, we believe that NSBB might present beneficial properties, as NSBB prevents acute variceal bleeding, are associated with a lower liver cancer mortality rate and may reduce HCC occurrence.2,3 Moreover, PHT is associated with worse outcome after locoregional treatment, such as liver decompensation and ascites occurrence that might preclude the access to further HCC treatment. It is therefore legitimate to question the prescription of NSBB to limit liver function worsening in patients at risk, as proposed by Baveno VII consensus.4 In addition, no negative effects of the use of NSBB have been demonstrated. The other major point is the diagnosis of PHT in HCC patients since even the use of the HVPG, considered as the gold standard to diagnose PHT, does not seem to be adapted in this patient population. Indeed, in our series of BCLC-0/A, patients with HVPG <10 mm Hg, 1/26 (3.8%) presented large-size EV (Se 88%, Sp 64%, PPV 36%, and NPV 96%) and 6/26 (23.1%) small EV (Se 67%, Sp 63%, PPV 56%, and NPV 73%). So, we are not in favor of prescribing NSBB without endoscopy, only in patients with baseline HVPG ≥10 mm Hg. Other techniques need to be developed, such as spleen stiffness measurement or imaging score for the proper diagnosis of PHT in HCC patients. Although Tripathi et al5 raised pertinent questions about the uncertainty of the literature regarding the use of NSBB in HCC patients, we still believe that the use of NSBB in patients with liver stiffness measurement of ≥25 kPa might improve their outcome and to date, no performant technique exists to diagnose PHT in this population of patients who appears as a major research issue.
Biomarker Changes Associated With Both Dulaglutide and Cardiovascular Events in the REWIND Randomized Controlled Trial: A Nested Case-Control Post Hoc Analysis
Authors: Hertzel C. Gerstein, Shun-Fu Lee, Guillaume Paré, M. Angelyn Bethel, Helen M. Colhoun, Anastasia Hoover, Mark Lakshmanan, Yanzhu Lin, Valentina Pirro, Hui-Rong Qian, Giacomo Ruotolo, Lars Ryden, Jonathan M. Wilson, Kevin L. Duffin
Journal: Diabetes Care (2023)

The glucagon-like peptide-1 receptor agonist dulaglutide reduced MACE in the Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) trial. This article expores the relationship of selected biomarkers to both dulaglutide and major adverse cardiovascular events (MACE).In this post hoc analysis, stored fasting baseline and 2-year plasma samples from 824 REWIND participants with MACE during follow-up and 845 matched non-MACE participants were analyzed for 2-year changes in 19 protein biomarkers. Two-year changes in 135 metabolites were also analyzed in 600 participants with MACE during follow-up and in 601 matched non-MACE participants. Linear and logistic regression models were used to identify proteins that were associated with both dulaglutide treatment and MACE. Similar models were used to identify metabolites that were associated with both dulaglutide treatment and MACE.Compared with placebo, dulaglutide was associated with a greater reduction or lesser 2-year rise from baseline in N-terminal prohormone of brain natriuretic peptide (NT-proBNP), growth differentiation factor 15 (GDF-15), high-sensitivity C-reactive protein, and a greater 2-year rise in C-peptide. Compared with placebo, dulaglutide was also associated with a greater fall from baseline in 2-hydroxybutyric acid and a greater rise in threonine (P < 0.001). Increases from baseline in two of the proteins (but neither metabolite) were associated with MACE, including NT-proBNP (OR 1.267; 95% CI 1.119, 1.435; P < 0.001) and GDF-15 (OR 1.937; 95% CI 1.424, 2.634; P < 0.001).Dulaglutide was associated with a reduced 2-year rise from baseline of NT-proBNP and GDF-15. Higher rises of these biomarkers were also associated with MACE.
Disrupting the phase separation of KAT8–IRF1 diminishes PD-L1 expression and promotes antitumor immunity
Authors: Yuanzhong Wu, Liwen Zhou, Yezi Zou, Yijun Zhang, Meifang Zhang, Liping Xu, Lisi Zheng, Wenting He, Kuai Yu, Ting Li, Xia Zhang, Zhenxuan Chen, Ruhua Zhang, Penghui Zhou, Nu Zhang, Limin Zheng, Tiebang Kang
Journal: Nature Cancer (2023)

Abstract Immunotherapies targeting the PD-1/PD-L1 axis have become first-line treatments in multiple cancers. However, only a limited subset of individuals achieves durable benefits because of the elusive mechanisms regulating PD-1/PD-L1. Here, we report that in cells exposed to interferon-γ (IFNγ), KAT8 undergoes phase separation with induced IRF1 and forms biomolecular condensates to upregulate PD-L1. Multivalency from both the specific and promiscuous interactions between IRF1 and KAT8 is required for condensate formation. KAT8–IRF1 condensation promotes IRF1 K78 acetylation and binding to the CD247 (PD-L1) promoter and further enriches the transcription apparatus to promote transcription of PD-L1 mRNA. Based on the mechanism of KAT8–IRF1 condensate formation, we identified the 2142–R8 blocking peptide, which disrupts KAT8–IRF1 condensate formation and consequently inhibits PD-L1 expression and enhances antitumor immunity in vitro and in vivo. Our findings reveal a key role of KAT8–IRF1 condensates in PD-L1 regulation and provide a competitive peptide to enhance antitumor immune responses.
Bacterial proton motive force as an unprecedented target to control antimicrobial resistance
Authors: Bingqing Yang, Ziwen Tong, Jingru Shi, Zhiqiang Wang, Yuan Liu
Journal: Medicinal Research Reviews (2023)

Novel antibacterial therapies are urgently required to tackle the increasing number of multidrug-resistant pathogens. Identification of new antimicrobial targets is critical to avoid possible cross-resistance issues. Bacterial proton motive force (PMF), an energetic pathway located on the bacterial membrane, crucially regulates various biological possesses such as adenosine triphosphate synthesis, active transport of molecules, and rotation of bacterial flagella. Nevertheless, the potential of bacterial PMF as an antibacterial target remains largely unexplored. The PMF generally comprises electric potential (ΔΨ) and transmembrane proton gradient (ΔpH). In this review, we present an overview of bacterial PMF, including its functions and characterizations, highlighting the representative antimicrobial agents that specifically target either ΔΨ or ΔpH. At the same time, we also discuss the adjuvant potential of bacterial PMF-targeting compounds. Lastly, we highlight the value of PMF disruptors in preventing the transmission of antibiotic resistance genes. These findings suggest that bacterial PMF represents an unprecedented target, providing a comprehensive approach to controlling antimicrobial resistance.
Error in Key Points, Main Text, and Funding/Support
Journal: JAMA Network Open (2023)

Eduard Mension, MD, MSc; Inmaculada Alonso, MD, PhD; Sònia Anglès-Acedo, MD, PhD; Cristina Ros, MD, PhD; Jorge Otero, PhD; Álvaro Villarino, MSc; Ramon Farré, PhD; Adela Saco, MD, PhD; Naiara Vega, BSC; Natalia Castrejón, MD; Jaume Ordi, MD, PhD; Natalia Rakislova, MD, PhD; Marta Tortajada, MD; Isabel Matas, MD; Sílvia Gómez, MD; Laura Ribera, MD; Camil Castelo-Branco, MD, PhD
The important but difficult exercise of getting valid descriptive skin cancer data
Authors: Esther de Vries
Journal: British Journal of Dermatology (2023)

Journal Article The important but difficult exercise of getting valid descriptive skin cancer data Get access Esther de Vries Esther de Vries Department of Clinical Epidemiology and Biostatistics, Pontificia Universidad Javeriana, Bogotá, ColombiaGlobal Initiative for the Development of Cancer Registries Correspondence: Esther de Vries. Email: estherdevries@javeriana.edu.co https://orcid.org/0000-0002-5560-2258 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 188, Issue 6, June 2023, Page 693, https://doi.org/10.1093/bjd/ljad065 Published: 10 March 2023 Article history Received: 23 February 2023 Published: 10 March 2023 Accepted: 17 March 2023 Corrected and typeset: 28 March 2023
Infectious complications of bispecific antibody therapy in patients with multiple myeloma
Authors: Beatrice Z. Sim, Anthony Longhitano, Jeremy Er, Simon J. Harrison, Monica A. Slavin, Benjamin W. Teh
Journal: Blood Cancer Journal (2023)

Rhinovirus/enterovirus (n = 8), influenza (n = 1), adenovirus (n = 4), COVID-19 (n = 2).4 BK virus (n = 1), cytomegalovirus (n = 4), herpes simplex virus 2 (n = 1), Epstein Barr virus (n = 1). 5Mycobacterium avium complex (n = 1).
Effect of Financial Incentives and Default Options on Food Choices of Adults With Low Income in Online Retail Settings
Authors: Pasquale E. Rummo, Christina A. Roberto, Lorna E. Thorpe, Andrea B. Troxel, Brian Elbel
Journal: JAMA Network Open (2023)

Importance Despite recent growth in online redemption of Supplemental Nutrition Assistance Program (SNAP) benefits, no previous work has tested the impact of economic and behavioral economic strategies on food purchasing behaviors in an online grocery retail setting among adults with low income. Objective To examine the extent to which financial incentives and default shopping cart options influence fruit and vegetable purchases. Design, Setting, and Participants This randomized clinical trial used an experimental online grocery store for adults who currently or have ever received SNAP benefits. From October 7 to December 2, 2021, participants were instructed to shop for a week’s worth of groceries for their household, with a budget tailored to household size; no payment was taken. Interventions Random assignment to 1 of 4 conditions: no intervention, 50% discount on eligible fruits and vegetables, prefilled shopping carts with tailored fruit and vegetable items (ie, default options), or a combination of the discount and default options. Main Outcomes and Measures The primary outcome was the percentage of nondiscounted dollars spent on eligible fruit and vegetables per basket. Results Of 2744 participants, mean (SD) age was 46.7 (16.0) years, and 1447 (52.7%) identified as women. A total of 1842 participants (67.1%) reported currently receiving SNAP benefits and 1492 (54.4%) reported shopping online for groceries in the previous 12 months. Participants spent a mean (SD) 20.5% (23.5%) of total dollars on eligible fruits and vegetables. Compared with no intervention, those in the discount condition spent 4.7% (98.3% CI, 1.7%-7.7%) of more total dollars on eligible fruits and vegetables; those in the default condition, 7.8% (98.3% CI, 4.8%-10.7%) more; and those in the combination condition, 13.0% (98.3% CI, 10.0%-16.0%) more ( P &amp;amp;lt; .001 for all). There was no difference between the discount and the default conditions ( P = .06), but the effect in the combination condition was significantly larger than both discount and default conditions ( P &amp;amp;lt; .001). Default shopping cart items were purchased by 679 participants (93.4%) in the default condition and 655 (95.5%) in the combination condition, whereas 297 (45.8%) in the control and 361 (52.9%) in the discount conditions purchased those items ( P &amp;amp;lt; .001). No variation was observed by age, sex, or race and ethnicity, and results were similar when those who reported never shopping online for groceries were excluded. Conclusions and Relevance In this randomized clinical trial, financial incentives for fruits and vegetables and default options, especially in combination, led to meaningful increases in online fruit and vegetable purchases among adults with low income. Trial Registration ClinicalTrials.gov Identifier: NCT04766034
License to kill: Retinoic acid programs T cells for tissue residency
Authors: Maximilian Heeg, Ananda W. Goldrath
Journal: The Journal of Experimental Medicine (2023)

In this issue of JEM, Qiu et al. (2023. J. Exp. Med. https://doi.org/10.1084/jem.20210923) show that retinoic acid signaling during priming in the mesenteric lymph node licenses CD8+ T cells to develop into small intestinal tissue-resident memory cells, a finding that provides key insights into tissue-specific vaccination strategies.
Screening of liver cancer with abbreviated MRI
Authors: Maxime Ronot, Pierre Nahon, Jordi Rimola
Journal: Hepatology (2023)

Current recommendations for the surveillance of HCC are based on the semiannual liver ultrasound (with or without serum alpha-fetoprotein) in patients with cirrhosis and in subgroups with chronic hepatitis B infection. However, the sensitivity of this strategy is suboptimal for the detection of early-stage tumors, especially in obese patients, due to interoperator variability and poor adherence. The detection rate of focal liver lesions is excellent with MRI, making it the best alternative candidate for surveillance. However, performing a full contrast-enhanced MRI is unrealistic because of limited availability and health economics. Abbreviated MRI (AMRI) corresponds to the acquisition of a limited number of sequences with a high detection rate. The theoretical benefits of AMRI are a reduced acquisition time (≤10 min) with improved time-effectiveness and cost-effectiveness compared with conventional MRI, and greater accuracy than ultrasound. Numerous protocols may be performed, including T1-weighted, T2-weighted, and DWI sequences, with or without contrast administration. Although published studies report promising per-patient results, they should be interpreted with caution. Indeed, most studies were simulated, retrospectively reviewing a subset of sequences in relatively small populations who underwent a full MRI. They also included groups that were not representative of screening populations. In addition, most were published by Asian groups, with at-risk populations that were different from Western populations. There are no existing longitudinal studies that directly compare the different AMRI approaches or AMRI to ultrasound. Finally, it is possible that 1 approach will not fit all patients and that strategies should be tailored to the risk of HCC, in particular in relation to the cost and availability of AMRI. Several trials are ongoing to evaluate these questions.
Association of Breast Cancer Family History With Breast Density Over Time in Korean Women
Authors: Thi Xuan Mai Tran, Yoosoo Chang, Soyeoun Kim, Huiyeon Song, Seungho Ryu, Boyoung Park
Journal: JAMA Network Open (2023)

Importance Evidence suggests that women with a family history of breast cancer (FHBC) in first-degree relatives have a higher level of breast density; however, studies of premenopausal women remain limited. Objective To investigate the association between FHBC and mammographic breast density and breast density changes among premenopausal women. Design, Setting, and Participants This retrospective cohort study used population-based data obtained from the National Health Insurance Service–National Health Information Database of Korea. We included premenopausal women aged 40 to 55 years who underwent mammography for breast cancer screening once between January 1, 2015, and December 31, 2016 (n = 1 174 214), and women who underwent mammography twice (first in 2015-2016 and again between January 1, 2017 and December 31, 2018) (n = 838 855). Exposures Family history of breast cancer was assessed using a self-reported questionnaire, which included information on FHBC in the mother and/or sister. Main Outcomes and Measures Breast density, based on the Breast Imaging Reporting and Data System, was categorized as dense (heterogeneously or extremely dense) and nondense (almost entirely fat or scattered fibroglandular areas). Multivariate logistic regression was used to assess the association among FHBC, breast density, and changes in breast density from the first to second screening. Data analysis was performed from June 1 to September 31, 2022. Results Of the 1 174 214 premenopausal women, 34 003 (2.4%; mean [SD] age, 46.3 [3.2] years) reported having FHBC among their first-degree relatives, and 1 140 211 (97.1%; mean [SD] age, 46.3 [3.2] years) reported no FHBC. Odds of having dense breasts was 22% higher (adjusted odds ratio [aOR], 1.22; 95% CI, 1.19-1.26) in women with FHBC than in women without FHBC, and the association varied by affected relatives: mother alone (aOR, 1.15; 95% CI, 1.10-1.21), sister alone (aOR, 1.26; 95% CI, 1.22-1.31), and both mother and sister (aOR, 1.64; 95% CI, 1.20-2.25). Among women with fatty breasts at baseline, the odds of developing dense breasts was higher in women with FHBC than in those without FHBC (aOR, 1.19; 95% CI, 1.11-1.26), whereas among women with dense breasts, higher odds of having persistently dense breasts were observed in women with FHBC (aOR, 1.11; 95% CI, 1.05-1.16) than in those without FHBC. Conclusions and Relevance In this cohort study of premenopausal Korean women, FHBC was positively associated with an increased incidence of having increased or persistently dense breasts over time. These findings suggest the need for a tailored breast cancer risk assessment for women with FHBC.
Differential response of HBV envelope-specific CD4+ T cells is related to HBsAg loss after stopping nucleos(t)ide analogue therapy
Authors: Yongyin Li, Chunhua Wen, Shuqin Gu, Weibin Wang, Ling Guo, Chris Kafai Li, Xuan Yi, Yang Zhou, Zheyu Dong, Xin Fu, Shihong Zhong, Yuhao Wang, Kuiyuan Huang, Junhua Yin, Chunxiu Zhong, Xieer Liang, Rong Fan, Haitao Chen, Deke Jiang, Xiaoyong Zhang, Jian Sun, Libo Tang, Jie Peng, Jinlin Hou
Journal: Hepatology (2023)

Background and Aims: Long-term maintenance of viral control, even HBsAg loss, remains a challenge for chronic hepatitis B (CHB) patients undergoing nucleos(t)ide analogue (NA) discontinuation. This study aimed to investigate the relationship between HBV-specific T cell responses targeting peptides spanning the whole proteome and clinical outcomes in CHB patients after NA discontinuation. Approach and Results: Eighty-eight CHB patients undergoing NA discontinuation were classified as responders (remained relapse-free up to 96 wk) or relapsers (relapsed patients who underwent NA re-treatment for up to 48 weeks and re-achieved stable viral control). HBV-specific T cell responses were detected at baseline and longitudinally throughout follow-up. We found responders had a greater magnitude of HBV Polymerase (Pol)-specific T cell responses than relapsers at baseline. After long-term NA discontinuation, simultaneously enhanced HBV Core- and Pol-induced responses were observed in responders. Particularly, responders with HBsAg loss possessed enhanced HBV Envelope (Env)-induced responses after short and long-term follow-up. Notably, CD4+T cells accounted for the predominance of HBV-specific T cell responses. Correspondingly, CD4-deficient mice showed attenuated HBV-specific CD8+T cell responses, reduced HBsAb-producing B cells, and delayed HBsAg loss; in contrast, in vitro addition of CD4+T cells promoted HBsAb production by B cells . Additionally, interleukin (IL)-9, rather than PD-1 blockade, enhanced HBV Pol-specific CD4+T cell responses. Conclusion: HBV-specific CD4+T cell responses induced by the targeted peptide possess specificities for long-term viral control and HBsAg loss in CHB patients undergoing NA discontinuation, indicating that CD4+T cells specific for distinct HBV antigens may endow with divergent antiviral potential. Export